The human fetus and newborn are unusually susceptible to infection with a wide variety of pathogens; current therapy for many of these infections is associated with unacceptable morbidity and mortality. Functional deficiencies of mononuclear phagocytes (MPhi) from newborns contribute to a similar susceptibility in newborn rodents and rabbits. Our ongoing studies with human placental MPhi suggest that human fetal and newborn MPhi have similar deficiencies, and that such deficiencies may be partly reversed by exposure to lymphokines. This proposal will extend the work performed during the current grant period. I am seeking to provide a frame of reference for comparing human placental MPhi function to that of primate newborn MPhi isolated from certain anatomic sites; placenta, cord blood, alveolar and liver (Kuppfer cells). The biological activity of these cells will be compared to human placental and cord blood MPhi and to MPhi derived from peripheral blood of adults humans and to blood alveolar and liver MPhi from adult primates. The ability of these MPhi to phagocytose or absorb, and to kill or restrict intracellular replication of LIsteria, herpes simplex and group B streptococcus (which are major perinatal pathogens) will be studied. The role of oxidative and non-oxidative (lysosomal) mechanisms and interferon in mediating antimicrobial activity of these MPhi will be assessed. We will examine the hypothesis that the antimicrobial function of certain of these MPhi can be augmented by immunomodulators (lymphokines and aminobutyryl muramyl dipeptide). Liposomes will be evaluated as a potential vehicle for delivery immunomodulators to MPhi. These studies, by increasing our understanding of perinatal-neonatal MPhi antimicrobial function, may allow future treatment of perinatal infections to be directed at reversing deficiencies in host cellular defense mechanisms, in addition to conventional antimicrobial therapy.